Endoluminal Biopsy for Vein of Galen Malformation.

BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to ∼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.

Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers.

Pathogenic germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer is the most common cancer in LFS females. We performed first of its kind multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC. Nearly all LFS-BC underwent biallelic loss of TP53 with no recurrent oncogenic variants except ERBB2 (HER2) amplification. Compared to sporadic BC, in situ and invasive LFS-BC exhibited a high burden of short amplified aneuploid segments (SAAS). Pro-apoptotic p53 target genes BAX and TP53I3 failed to be up-regulated in LFS-BC as was seen in sporadic BC compared to normal breast tissue. LFS-BC had lower CD8+ T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression from in situ to invasive BC was marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue.

Global Economic Evaluation of the Reported Costs of Deep Brain Stimulation.

INTRODUCTION: Despite the known benefits of deep brain stimulation (DBS), the cost of the procedure can limit access and can vary widely. Our aim was to conduct a systematic review of the reported costs associated with DBS, as well as the variability in reporting cost-associated factors to ultimately increase patient access to this therapy. METHODS: A systematic review of the literature for cost of DBS treatment was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase databases were queried. Olsen & Associates (OANDA) was used to convert all reported rates to USD. Cost was corrected for inflation using the US Bureau of Labor Statistics Inflation Calculator, correcting to April 2022. RESULTS: Twenty-six articles on the cost of DBS surgery from 2001 to 2021 were included. The median number of patients across studies was 193, the mean reported age was 60.5 ± 5.6 years, and median female prevalence was 38.9%. The inflation- and currency-adjusted mean cost of the DBS device was USD 21,496.07 ± USD 8,944.16, the cost of surgery alone was USD 14,685.22 ± USD 8,479.66, the total cost of surgery was USD 40,942.85 ± USD 17,987.43, and the total cost of treatment until 1 year of follow-up was USD 47,632.27 ± USD 23,067.08. There were no differences in costs observed across surgical indication or country. CONCLUSION: Our report describes the large variation in DBS costs and the manner of reporting costs. The current lack of standardization impedes productive discourse as comparisons are hindered by both geographic and chronological variations. Emphasis should be put on standardized reporting and analysis of reimbursement costs to better assess the variability of DBS-associated costs in order to make this procedure more cost-effective and address areas for improvement to increase patient access to DBS.

Efficacy of a prolonged stability melphalan formulation for intra-arterial treatment of retinoblastoma.

BACKGROUND: Melphalan, which is poorly soluble at room temperature, is widely used for the treatment of retinoblastoma by selective ophthalmic artery infusion. Evomela, a propylene glycol-free formulation of melphalan with improved solubility and stability, has recently been used as an alternative.To compare the safety and efficacy of Evomela with standard-formulation melphalan (SFM) in the treatment of retinoblastoma by selective ophthalmic artery infusion. METHODS: We performed a retrospective case-control study of patients with retinoblastoma undergoing selective ophthalmic artery infusion with SFM or Evomela at a single institution. Cycle-specific percent tumor regression (CSPTR) was estimated by comparing photos obtained during pretreatment examination under anesthesia (EUA) with those obtained during post-treatment EUA 3-4 weeks later. CSPTR, ocular salvage rates, complication rates, operation times (unadjusted and adjusted for difficulty of ophthalmic artery catheterization), and intraprocedural dose expiration rates were compared between Evomela- and SFM-treated groups. Univariate and multivariate analyses were performed. RESULTS: Ninety-seven operations (melphalan: 45; Evomela: 52) for 23 patients with 27 retinoblastomas were studied. The ocular salvage rate was 79% in the SFM-treated group and 69% in the Evomela-treated group. Multivariate regression controlling for tumor grade, patient age, and treatment history revealed no significant differences in ocular salvage rate, CSPTR, complication rates, or operation times. Although the dose expiration rate was higher for the SFM-treated group, the difference was not statistically significant. Notably, there were no ocular or cerebral ischemic complications. CONCLUSION: Evomela has non-inferior safety and efficacy relative to SFM when used for the treatment of retinoblastoma by selective ophthalmic artery infusion.

The cost of a plastic surgery team assisting with cranioplasty.

OBJECTIVES: Cranioplasty is a commonly performed neurosurgical procedure that restores cranial anatomy. While plastic surgeons are commonly involved with cranioplasties, the cost of performing a cranioplasty with neurosurgery alone (N) vs. neurosurgery and plastic surgery (N + P) is unknown. METHODS: A single-center, multi-surgeon, retrospective cohort study was undertaken on all cranioplasties performed from 2012 to 22. The primary exposure variable of interest was operating team, comparing N vs. N + P. Cost data was inflation-adjusted to January 2022 using Healthcare Producer Price Index as calculated by the US Bureau of Labor Statistics. RESULTS: 186 patients (105 N vs. 81 N + P) underwent cranioplasties. The N + P group has a significantly longer length-of-stay (LOS) 4.5 ± 1.6days, vs. 6.0 ± 1.3days (p < 0.001), but no significant difference in reoperation, readmission, sepsis, or wound breakdown. N was significantly less expensive than N + P during both the initial cranioplasty cost ($36,739 ± $4592 vs. $41,129 ± $4374, p 0.014) and total cranioplasty costs including reoperations ($38,849 ± $5017 vs. $53,134 ± $6912, p < 0.001). Univariable analysis (threshold p = 0.20) was performed to justify inclusion into a multivariable regression model. Multivariable analysis for initial cranioplasty cost showed that sepsis (p = 0.024) and LOS (p = 0.003) were the dominant cost contributors compared to surgeon type (p = 0.200). However, surgeon type (N vs. N + P) was the only significant factor (p = 0.011) for total cost including revisions. CONCLUSIONS: Higher costs to N + P involvement without obvious change in outcomes were found in patients undergoing cranioplasty. Although other factors are more significant for the initial cranioplasty cost (sepsis, LOS), surgeon type proved the independent dominant factor for total cranioplasty costs, including revisions.

Oral health and functional outcomes following mechanical thrombectomy for ischemic stroke.

BACKGROUND: An association between poor dentition and the risk of ischemic stroke has previously been reported in the literature. In this study we assessed oral hygiene (OH), including tooth loss and the presence of dental disease, to determine if an association exists with functional outcomes following mechanical thrombectomy (MT) for large-vessel ischemic stroke. METHODS: A retrospective review was conducted of consecutive adult patients at a single comprehensive stroke center who underwent MT from 2012 to 2018. Inclusion criteria included availability of CT imaging to radiographically assess OH. A multivariate analysis was performed, with the primary outcome being 90-day post-thrombectomy modified Rankin Scale (mRS) score >2. RESULTS: A total of 276 patients met the inclusion criteria. The average number of missing teeth was significantly higher in patients with a poor functional outcome (mean (SD) 10 (11) vs 4 (6), p<0.001). The presence of dental disease was associated with poor functional outcome, including cavities (21 (27%) vs 13 (8%), p<0.001), periapical infection (18 (23%) vs 11 (6.7%), p<0.001), and bone loss (27 (35%) vs 11 (6.7%), p<0.001). Unadjusted, missing teeth was a univariate predictor of poor outcome (OR 1.09 (95% CI 1.06 to 1.13), p<0.001). After adjustment for recanalization scores and use of tissue plasminogen activator (tPA), missing teeth remained a predictor of poor outcome (OR 1.07 (95% CI 1.03 to 1.11), p<0.001). CONCLUSION: Missing teeth and the presence of dental disease are inversely correlated with functional independence following MT, independent of thrombectomy success or tPA status.

Characterizing internet search patterns for neurologic and neurosurgical conditions following celebrity diagnosis.

Social media and internet platforms have become significant drivers of mass-information. Highly publicized events, such as John McCain's announcement of his glioblastoma diagnosis, often drive national public interest in medical topics. Improved understanding of the temporality of interest spikes as well as the nature of the information that garners attention from outside the medical community can help inform ways in which the medical community can boost awareness of (and interest in) the field of neurosurgery. We utilized the "explore topics" feature on Google Trends to obtain web, news, and YouTube search data from May 1, 2015, to May 1, 2019 for the terms "glioblastoma," "brain tumor," "stroke," and "multiple sclerosis" to identify periods of visibly increased search interest. Search results for "glioblastoma" showed significantly elevated average interest during the period of July 3-23, 2017, as compared to that generated since this specific time period (42.6 vs. 8.73, P<0.001). This increased search activity therefore directly correlated with John McCain's public announcement of his glioblastoma diagnosis, and a similar search interest spike was evident using the search term "brain tumor" (87.3 vs. 64.2, P<0.001). Search results for "multiple sclerosis" showed - as a result of the online buzz created by Selma Blair's battle with the disease - significantly elevated average interest from October 8, 2018, to October 28, 2018, and February 11, 2019, to March 3, 2019, when compared to the average interest of the remaining time (59 vs. 40.16, P<0.001 and 69 vs. 40.16, P<0.001). Finally, there were no corresponding elevations in YouTube search interest for any of the terms associated with increased interest on Google Trends. Following major events related to the neurological disease of public figures there is an expected rise in Google search interest relevant to these topics. Our findings suggest that there is an optimal window of approximately 2 weeks following each of these events for activist and clinical groups to publicize their desired message, and for the field of neurosurgery and neurological science to increase public awareness regarding specific diseases, with a regression to baseline interest by 4 months following the event.

It's not all White: Implicit Racial Bias in Imagery Used in Plastic Surgery Resident Education.

OBJECTIVE: Plastic surgery education relies heavily on images featuring patient skin tone; while images can be useful representations, it is highly susceptible to implicit bias, a known contributor to healthcare disparities. Using skin tone as a proxy, this study evaluates patient representation in images used in the American Society of Plastic Surgery Resident Education Curriculum. DESIGN: Color photographs, graphics, and videos featured in the American Society of Plastic Surgery "Course Materials" for each module were categorized using the Fitzpatrick scale (I-II, III-IV, or V-VI) by six reviewers. Proportional data and average number ± standard deviation of photos and graphics for each category were reported. Significant difference between Fitzpatrick I to II and V to VI was investigated via a one-way analysis of variance with a Tukey's post-test to adjust for multiple comparisons. RESULTS: An average of 1861 photographs and 237 graphics were assessed with 82% (1518 ± 25.11) of photos and 97% (231 ± 24.45) of graphics categorized as Fitzpatrick I to II. A one-way analysis of variance with a Tukey's post-test demonstrates a statistical difference between images and graphics categorized as Fitzpatrick I to II and Fitzpatrick V to VI (p < 0.001). CONCLUSIONS: Our data reveals an opportunity to improve racial representation in resident education. When 76% of patients in the United States are white and 13% are Black, our findings demonstrate both an unequal and unrepresentative distribution of photos and graphics of non-white patients. Residency is a formative time in a surgeon's career and therefore, exposure to accurate representation of a diverse patient population is of the utmost importance.

Management of postradiation late hemorrhage following treatment for HPV-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Acute oropharyngeal hemorrhage is a serious complication for patients with oropharyngeal squamous cell carcinoma (OPSCC), particularly in patients with a history of radiation therapy (RT). METHODS: Retrospective case series from at a tertiary care center for treated patients with HPV-positive OPSCC presenting with oropharyngeal hemorrhage. RESULTS: Median time from completion of chemoradiation to first hemorrhagic event was 186 days (range 66-1466 days). Seven patients (58%) required intervention to secure their airway. All patients were evaluated for endovascular intervention, six (50%) were embolized. Eight patients (67%) had a second hemorrhagic event; median time to second bleed was 22 days (range 3-90 days). CONCLUSIONS: Acute oropharyngeal hemorrhage is a sequelae following treatment for HPV-positive OPSCC. The majority of bleeds occurred within a year of completion of treatment. While more research is needed to determine optimal treatment paradigms, endovascular intervention should be considered, even if noninvasive imaging does not demonstrate active bleeding.

Formation of a de novo intracranial arteriovenous fistula in a child with PTEN hamartoma tumor syndrome.

PURPOSE: Dural arteriovenous fistulae (dAVF) are an uncommon feature of PTEN hamartoma tumor syndrome (PHTS). We report a case of an adolescent male diagnosed with PHTS following the treatment of multiple intracranial dAVF to emphasize the association of vascular anomalies with this disorder and discuss potential implications. CASE REPORT: An adolescent male presented with bilateral proptosis secondary to intracranial venous hypertension. Workup revealed the presence of a complex intracranial dAVF which was treated with several embolization procedures. Following treatment, a de novo dAVF was identified on surveillance imaging. A genetic workup revealed a pathogenic mutation in PTEN consistent with a diagnosis of PHTS. CONCLUSIONS: Recognition that PHTS may be associated with dAVF, and potentially delayed spontaneous formation of dAVF, is critically important due to the potential for devastating yet preventable neurologic sequelae.

An Examination of Standardized Letters of Recommendation Rating Scales Among Neurosurgical Residency Candidates During the 2020-2021 Application Cycle.

BACKGROUND: Letters of recommendation (LORs) are historically an important, though subjective, component of the neurosurgery residency application process. Standardized LORs (SLORs) were introduced during the 2020 to 2021 application cycle. The intent of SLORs is to allow objective comparison of applicants and to reduce bias. OBJECTIVE: To examine the utility of SLORs during this application cycle. We hypothesized that "grade inflation" and poor inter-rater reliability, as described by other specialties using SLORs, would limit the utility of SLORs in their current form. METHODS: This cross-sectional study analyzed all SLORs submitted to a single neurosurgery residency program over the 2020 to 2021 cycle. Data from 7 competency domains and the overall rating were recorded and stratified by academic category of letter writer. Inter-rater reliability was evaluated using Krippendorff's alpha. RESULTS: One or more SLORs was submitted as part of 298 of 393 applications (76%). Approximately 58.3% of letters written by neurosurgery chairpersons rated a given applicant as being within the top 5% across all competencies. Approximately 44.4% of program director letters similarly rated applicants as amongst the top 5%, while 73.2% and 81.4% of letters by other neurosurgeons and general surgery evaluators, respectively, rated applicants in the top 5%. Inter-rater reliability was poor (<0.33) in all rating categories, including overall (α = 0.18). CONCLUSION: The utility of the first iteration of SLORs in neurosurgery applications is undermined by significant "grade inflation" and poor inter-rater reliability. Improvements are necessary for SLORs if they are to provide meaningful information in future application cycles.

A 15-Year Review of Iatrogenic Burn Injuries in an Academic Public Hospital.

Hospital-acquired burn injuries can result in increased length of hospitalization, costs of stay, and potential for additional procedures. The aim of this study is to describe iatrogenic burn injuries over a 15-year period at an academic public hospital system. Data was collected from January 2004 to June 2019. Data included time of injury, hospital location, mechanism, level of harm caused, and anatomic location of the injury. Demographic information included patient age, gender, body mass index, payer status, primary admission diagnosis and length of stay. 122 patients were identified through an internal hospital database that tracked reported injuries. Incidence was highest between 2005-2012 (12.3 ± 4.1 per year) as compared to 2013-2019 (2.9 ± 2.1 per year). A majority (77%) resulted in harm caused to the patient. Most (41%) of the injuries occurred on the general medical floors, followed by the operating room (33.6%). The most common etiology was scald (23%), followed by electrocautery (14.8%). Five of the injuries resulted in burn consults, although none of these patients required surgery. Iatrogenic burns appear to be decreasing. While a majority were reported to have caused patient harm, none were serious enough to warrant surgery. Most injuries occurred on the medical floors with a scald mechanism. This review presents an opportunity to emphasize in-hospital burn prevention, as well as an opportunity for the burn team to affect change in concert with hospital administration.

Association of asymptomatic hemorrhage after endovascular stroke treatment with outcomes.

BACKGROUND: Intracerebral hemorrhage (ICH) occurs in ~20%-30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes. METHODS: In this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0-2 vs 3-6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models. RESULTS: Of 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53-1.35], P=0.55, aOR 0.84 [0.48-1.44], P=0.53 for 90-day mRS 0-2; OR 0.77 [0.48-1.23], P=0.34, aOR 0.72 [0.43-1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48-1.26], P=0.33 for 90-day mRS 0-2; OR 0.89 [0.69-1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01). CONCLUSIONS: aICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.

Angiographic investigation of orbital vascular variations in the rabbit and implications for endovascular intra-arterial chemotherapy models.

BACKGROUND: The New Zealand White rabbit (NZWR) is the first small-animal experimental model of intra-arterial chemotherapy (IAC) for retinoblastoma treatment. The NZWR has dual ophthalmic arteries (OA): the external OA (EOA) arises from the external carotid artery and the internal OA (IOA) from the internal carotid artery. We describe the technique that we have refined for OA catheterization in rabbits, and describe the angioanatomical variations in the OA supply to the NZWR eye and implications for IAC delivery, which were identified as part of a larger project exploring IAC effects in a rabbit retinoblastoma model. METHODS: We developed techniques to perform angiography of the external and internal carotid arteries and superselective angiography of the EOA and IOA in NZWR using transfemoral access and a microwire/microcatheter system. EOA and IOA supply to the eye was determined angiographically and recorded before selective OA catheterization and angiography. RESULTS: 114 rabbits underwent carotid angiographic evaluation and OA catheterization (161 total eyes evaluated, 112 right, 49 left). Most eyes had a single dominant arterial supply; either IOA or EOA. EOA was dominant in 73% (118/161), and IOA was dominant in 17% (27/161). Co-dominant supply was seen in 10% (16/161). Of the rabbits with bilateral OA catheterization, 25/47 (53%) had bilateral dominant EOA. CONCLUSION: Successful catheterization of the OA in the NZWR can be readily accomplished with nuanced technique. The external OA is the dominant arterial supply in the majority of NZWR eyes. These findings allow for successful reproduction of OA catheterization studies of IAC for retinoblastoma in NZWR.

Efficacy of decompressive craniectomy in the management of intracranial pressure in severe traumatic brain injury.

Traumatic brain injury (TBI) is a common cause of permanent disability for which clinical management remains suboptimal. Elevated intracranial pressure (ICP) is a common sequela following TBI leading to death and permanent disability if not properly managed. While clinicians often employ stepwise acute care algorithms to reduce ICP, a number of patients will fail medical management and may be considered for surgical decompression. Decompressive craniectomy (DC) involves removing a component of the bony skull to allow cerebral tissue expansion in order to reduce ICP. However, the impact of DC, which is performed in the setting of neurological instability, ongoing secondary injury, and patient resuscitation, has been challenging to study and outcomes are not well understood. This review summarizes historical and recent studies to elucidate indications for DC and the nuances, risks and complications in its application. The pathophysiology driving ICP elevation, and the corresponding medical interventions for their temporization and treatment, are thoroughly described. The current state of DC - including appropriate injury classification, surgical techniques, concurrent medical therapies, mortality and functional outcomes - is presented. We also report on the recent updates from large randomized controlled trials in severe TBI (Decompressive Craniectomy [DECRA] and Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of ICP [RESCUEicp]), and recommendations for early DC to treat refractory ICP elevations in malignant middle cerebral artery syndrome. Limitations for DC, such as the equipoise between immediate reduction in ICP and clinically meaningful functional outcomes, are discussed in support of future investigations.

Burn in an Irradiated Prepectoral Breast Reconstruction: A Cautionary Tale.

Burns to breast reconstructions, both autologous and implant-based, are well described in the plastic surgery literature. The mechanism has often been contact; however, burns secondary to sun exposure have also been reported. With the increasing number of prepectoral breast reconstructions, including irradiated prepectoral reconstructions, we would like to highlight the increased susceptibility of these reconstructions to thermal and ultraviolet injury. We present the case of a patient who underwent prepectoral implant-based breast reconstruction years after irradiation, who subsequently developed full-thickness injury to her mastectomy flap after minor sun exposure. After weeks of daily wound care and hyperbaric oxygen treatments, the patient eventually reepithelialized over her exposed acellular dermal matrix tissue layer, allowing for implant salvage. Postmastectomy flaps overlying implants in the prepectoral plane are delicate; major burns can develop from minor thermal injury, even months after surgery. Irradiated prepectoral reconstruction patients should be educated about the susceptibility of their breast flaps to even minor burn injury and should maintain vigilance beyond the immediate postoperative period. It remains to be seen whether prepectoral reconstruction in an irradiated breast can be a viable, long-term option.

Vorinostat suppresses hypoxia signaling by modulating nuclear translocation of hypoxia inducible factor 1 alpha.

Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi. Through an in-vitro and in-vivo approach utilizing cell lines for hepatocellular carcinoma (HCC), osteosarcoma (OS), and glioblastoma (GBM), we demonstrate that SAHA potently inhibits HIF-a nuclear translocation via direct acetylation of its associated chaperone, heat shock protein 90 (Hsp90). In the presence of SAHA we found elevated levels of acetyl-Hsp90, decreased interaction between acetyl-Hsp90 and HIF-a, decreased nuclear/cytoplasmic HIF-α expression, absent HIF-α association with its nuclear karyopharyin Importin, and markedly decreased HIF-a transcriptional activity. These changes were associated with downregulation of downstream hypoxia molecules such as endothelin 1, erythropoietin, glucose transporter 1, and vascular endothelial growth factor. Findings were replicated in an in-vivo Hep3B HRE-Luc expressing xenograft, and were associated with significant decreases in xenograft tumor size. Altogether, this study highlights a novel mechanism of action of an important class of chemotherapeutic.

Congenital Malformations of the Central Nervous System in Rural Western Honduras: A 6-Year Report on Trends.

BACKGROUND: Central nervous system (CNS) malformations, including neural tube defects (NTDs), are the second most common type of birth defects worldwide and are major causes of childhood disability and mortality. We report the first analysis of birth prevalence in Western Honduras of CNS malformations including NTDs over 6 consecutive years. METHODS: Data from all patients with congenital CNS malformations and total live births for the period 2010-2015 were obtained through institution and regional registries from all 3 public referral hospitals in Western Honduras, representing 67 municipalities. Cases were identified using the International Classification of Diseases, Tenth Revision CNS malformation codes. Birth prevalence was calculated as cases per 10,000 live births. RESULTS: From 123,903 live births, 275 cases of CNS malformations were identified (54% females, 58% NTDs). Six-year birth prevalence of CNS malformations was 13.9-31.1. Spina bifida variants and anencephaly represented 80% and 19% of reported NTDs, respectively. Total 6-year prevalence of NTDs in Western Honduras was 7.0-17.4 over years studied. In 6 municipalities, average prevalence was >30 (maximum 49.0). CONCLUSION: This is the first study reporting disease burden of CNS malformations in Western Honduras. The nationwide birth prevalence of NTDs in rural Honduras may have decreased since the implementation of prenatal health policies in 2005. However, we identified regions with unexpectedly elevated prevalence, indicating high regional prevalence that could be targeted for improved preventive efforts, ultimately decreasing the burden of these conditions.

The Use of Vasopressors in Pedicled Flaps for Chest Wall Reconstruction.

INTRODUCTION: The effect of vasopressors on flaps remains controversial in the literature. Often, surgeons avoid vasopressors with the thought that vasoconstriction reduces flap perfusion resulting in flap loss. METHODS: A retrospective review was performed on patients who required chest wall reconstruction from 1998 to 2013. Patients were identified through the use of Current Procedural Terminology codes. The data collected included demographics, indications for surgery, prior debridement, preoperative albumin levels, and perioperative vasopressor use. Outcomes measures included flap survival, flap complications, reoperation rates, intensive care unit length of stay, and mortality. RESULTS: Of the 1220 patient records reviewed, 88 had chest reconstruction by a plastic surgeon. Twenty-one patient records were excluded due to incomplete data. One patient experienced complete flap loss; these data were excluded from statistical analysis. Fifty patients received perioperative vasopressors whereas 15 did not. There was no significant difference in flap survival or loss between groups who received perioperative vasopressors and those who did not receive vasopressors. Age, intensive care unit length of stay, flap complications, and reoperation rates were significantly higher in those with partial flap survival. CONCLUSIONS: Perioperative vasopressor use does not adversely affect the outcome of pedicled flaps for chest wall reconstruction. Further research is warranted to review the effects of vasopressor dose and type on pedicled flaps.

Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target.

Von Hippel-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the central nervous system (CNS), and are a leading cause of morbidity and mortality in VHL disease. Currently, surgical resection is the most effective way to manage symptomatic VHL-HBs. Surgically unresectable VHL-HBs or those in frail patients are challenging problems. Therapies targeting oncologic and vascular endothelial growth factor (VEGF) pathways have failed to demonstrate tumor control. Our experience and previous reports on VHL-HB avidity to somatostatin analogues suggested somatostatin receptor (SSTR) expression in VHL-HBs, offering an alternative therapeutic strategy. We explored this possibility by demonstrating consistent histologic expression of SSTR1, 2a, 4, and 5 in VHL-HBs. We found that somatostatin analogue octreotide induces apoptosis in VHL-HB stromal cells in a dose-dependent fashion by BAX - caspase-3 pathway unrelated to canonical VHL pathway. When administered to a patient with unresectable symptomatic suprasellar hemangioblastoma, octreotide resulted in tumor volume reduction, symptom stabilization, and tumor cytopenia on repeat 68Ga-DOTA-TATE positron emission tomography (PET) within 6 months, suggesting tumor infarction. We conclude that VHL-HBs harbor multiple SSTR subtypes that offer actionable chemo-therapeutic strategy for management of symptomatic, unresectable tumors by somatostatin analogue therapy.